Hematoporphyrin derivative (HpD) a fluorogenic compound, has been shown to be retained preferentially by various tumor tissues. Photoradiation of HpD-containing tissue results in the release of singlet oxygen which caused cellular destruction. Although application of HpD for detection and treatment of a number of human cancers has been reported, the status of the technique is still at its early stage of development. Many basic biological and technical problem remain, which if resolved, would greatly enhance the utility of HpD in tumor detection and treatments. The proposed project is designed to obtain information on action of HpD and to develop techniques for the application of HpD in the detection and treatment of transitional cell carcinoma of the bladder (TCC). Combinations of cultured tumor cells, tumor-bearing animals and patients with TCC will be used to carry out research in the following areas: 1. Interaction of HpD with tumor and normal cells: To elucidate the cellular and biochemical mechanisms for the preferential retention of HpD by TCC, to investigate the possible binding of HpD to proteins, to identify these proteins and their distribution in normal and tumor tissues, to examine the mechanisms of cell destructions by singlet oxygen, and to develop methods for the quantitative measurement of HpD in specimens. 2. HpD for detection of TCC: To explore the use of intravesical instillation as a more effective and safer means of HpD administration, to study the photobiology of the urothelium, to develop a fiber-optic instrument for detection of HpD in TCC, and to carry out tests in vitro and in vivo for the sensitivity and specificity of this instrument. 3. HpD for treatment of TCC: To define optimal conditions for HpD administration and specifications for an instrument that can deliver light of proper wavelength and intensity for destruction of TCC, and to evaluate the effectiveness and toxicity of this treatment as the basis for the development of a protocol for future trials in patients. This project has the potential of providing new, effective, safe, and inexpensive means of diagnosis and treatment of TCC, particularly of carcinoma-in-situ and superficial tumors.